title: Plasma cytokine levels and cytokine gene polymorphisms in Mexican patients during the influenza pandemic A(H1N1)pdm09.
abstract: BACKGROUND
  In Mexico, the initial severe cases of the 2009 influenza pandemic virus A (H1N1) [A(H1N1)pdm09] were detected in early March. The immune mechanisms associated with the severe pneumonia caused by infection with this new virus have not been completely elucidated. Polymorphisms in interleukin genes have previously been associated with susceptibility to infectious diseases due to their influence on cytokine production.
  
  
  OBJECTIVE
  The present case-control study was performed to compare several immunologic and genetic parameters of patients and controls during the initial phase of the pandemic.
  
  
  METHODS
  Sixty-five patients who were hospitalized due to infection with the influenza A(H1N1)pdm09 virus and 46 healthy controls were studied. A hemagglutination inhibition assay (HIA) was performed to measure anti-influenza antibody titers in these subjects. Protein levels of the cytokines interleukin (IL)-4, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNFα), interferon gamma (IFNγ), transforming growth factor beta (TGFβ)1 and TGFβ2 were quantified in plasma. Single nucleotide polymorphisms in IL6, IL10 and TNFα were also assessed.
  
  
  RESULTS
  Influenza patients had lower antibody titers and produced significantly higher levels of IL-6, IL-10 and TNFα than healthy controls. The frequencies of the TNFα -308G, IL-10 -592C and IL-10 -1082A alleles and the IL10 -1082(A/A) genotype were associated with susceptibility to severe disease, while the haplotypes TNFα AG and IL-10 GTA and GCA were associated with protection from severe disease [P=0.016, OR (CI)=0.11 (0.01-0.96); P=0.0187, OR (CI)=0.34 (0.13-0.85); P=0.013, OR (CI)=0.39 (0.18-0.83)].
  
  
  CONCLUSIONS
  This study demonstrates that the influenza A(H1N1)pdm09 patients and healthy controls have different profiles of immune parameters and that there is an association between IL-10 and TNFα polymorphisms and the outcome of this disease.
authors.affiliation: Hospital General Dr. Manuel Gea González, México, DF 14080, Mexico.
authors.forename: Joel
authors.initials: J
authors.lastname: Martinez-Ocaña
authors.forename: Angélica
authors.initials: A
authors.lastname: Olivo-Diaz
authors.forename: Tobías
authors.initials: T
authors.lastname: Salazar-Dominguez
authors.forename: Jesús
authors.initials: J
authors.lastname: Reyes-Gordillo
authors.forename: Cynthia
authors.initials: C
authors.lastname: Tapia-Aquino
authors.forename: Fernando
authors.initials: F
authors.lastname: Martínez-Hernández
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Manjarrez
authors.forename: Marco
authors.initials: M
authors.lastname: Antonio-Martinez
authors.forename: Araceli
authors.initials: A
authors.lastname: Contreras-Molina
authors.forename: Rafael
authors.initials: R
authors.lastname: Figueroa-Moreno
authors.forename: Rafael
authors.initials: R
authors.lastname: Valdez-Vazquez
authors.forename: Simón
authors.initials: S
authors.lastname: Kawa-Karasik
authors.forename: Patricia
authors.initials: P
authors.lastname: Rodríguez-Zulueta
authors.forename: Ana
authors.initials: A
authors.lastname: Flisser
authors.forename: Pablo
authors.initials: P
authors.lastname: Maravilla
authors.forename: Mirza
authors.initials: M
authors.lastname: Romero-Valdovinos
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood* / Q000235:genetics*; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000302:isolation & purification; D007251:Influenza, Human / Q000276:immunology* / Q000821:virology*; D008297:Male; D008800:Mexico; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D016207:Cytokines
keywords: A(H1N1)pdm09; Cytokine plasma levels; Cytokine polymorphism; HIA; Hemagglutination Inhibition assay; IL-10; Influenza; Pandemic A/H1N1